Abstract: In response to RFA-DA-17-019 we propose to establish a Coordinating Center for the NIDA Cohorts entitled “C3NPO” * to manage and stimulate use of the data generated to address high priority research on HIV/AIDS in the context of substance abuse. Our focus is cutting-edge science powered by the cohorts’ combined sample size of approximately 12,500 participants. We bring together a team of researchers with global leadership in substance use, HIV prevention, clinical science and co-morbidities, immunology, modeling, and bioethics to work with NIDA program scientists to stimulate the highest impact science across NIDA-funded cohorts that have compiled unique repositories of varied and rich data. Our proposal uniquely combines academic and professional research management expertise that will stimulate, manage, and support scientific collaboration. We will enable internal and external investigators to cultivate the data from these cohorts in new and innovative scientific directions. Our bioinformatics capacity is uniquely strong in the area of specimen management, having developed the industry gold standard software that will greatly facilitate sharing of specimens across the cohorts. Our leadership bridges NIDA’s interests with the perspectives and concerns of the cohorts by having a cohort PI/research scientist (Pamina Gorbach, University of California, Los Angeles) partnered with an experienced HIV network bioinformatics management leader (Suzanne Siminski, Frontier Science & Technology Research Foundation (FSTRF). We will leverage other funded research initiatives though our External Scientific Advisory Board (ESAB) such as NIDA-supported efforts to harmonize measures for substance use research and combine that with data linking strategies. We have the endorsement of all cohort PIs that Consortium leadership is best led from another cohort PI to enhance team science and support for our team as the leaders. The collaborative character of this proposing team offers the potential for new developments in bioinformatics techniques that allow integration of diverse and ever more massive sets of behavioral, clinical, and laboratory data for use by cohort and outside researchers. Thus, our proposal will address NIDA’s 2016-2020 Strategic Plan priority focus areas and cross-cutting themes (https://www.drugabuse.gov/about-nida/2016-2020-nida-strategic-plan) by leveraging technology, driving innovation, promoting collaboration, and encouraging data and resource sharing. The strategy will develop infrastructure that allows cross-disciplinary, large-scale analyses leading to the highest impact HIV science on substance use.